OBJECTIVE: The ultimate objective of this research is to establish an effective procedure whereby malignant cells can be eliminated from the liver by combined therapy while retaining satisfactory hepatic function. APPROACH: A proposed treatment scheme for curative irradiation of liver tumors will be tested in ACI rats. Currently, radiation therapy of liver tumors is limited by hepatic tolerance of radiation. Radiation doses sufficient to cure extensive intrahepatic tumors may cause a fatal radiation hepatitis with death from liver failure. The proposed treatment scheme will seek to overcome this limitation by stimulating the liver to produce new cells after half of the tumoricidal radiation dose has been administered. The stimulation will be provided, performing a partial hepatectomy (removing approximately 70% of the liver) which should result in regeneration of the liver mass within two weeks. The regenerated liver cells will therefore receive only one-half of the total dose and should be able to function normally. The tumor cells (and the original liver cells) will receive a full therapeutic radiation dose. Existing data on the effect of preoperative radiation and of post-operative radiation on the capacity of the liver to undergo regeneration indicate that the basic experimental rationale is feasible, although the effects of the combination of the two types of radiation have not been previously tested. We shall measure the effects of these treatments separately and then in combination in the ACI rat for both acute and chronic effects. We shall develop an intrahepatic tumor model system, using the Morris Hepatoma 3924A which has been developed from this strain, and then measure the effect of the combined treatments on the intrahepatic tumor cells. We shall determine dose-response relationships for single and fractionated irradiations by observing histological and functional effects at 1, 2 and 12 months post-therapy. Hepatic clearance of colloid and serum levels of alkaline phosphatase, SGOT and bilirubin will be measured.